Viruses used in vaccines can recombine—and get virulent

Outbreaks of new herpesvirus in poultry traced back to merged vaccine strains.

The first successful vaccines, like Jenner's smallpox vaccine and the first Salk vaccine against polio, were based on viruses that do not cause illness or severe symptoms. Vaccine development has since shifted largely to the use of proteins that are used by the disease-causing agents, but there are still some cases where a dead or attenuated virus is the most effective method of generating immunity.

The use of viruses for vaccines, however, has always come with a bit of a concern. When it comes to viruses, one-in-a-million events happen all the time, and evolution gives any viruses used in vaccines a lot to work with: many related viruses in the wild, and animal genomes that are littered with pieces of former viruses. Now, researchers have discovered a case where two different agricultural vaccines have recombined to create a new, virulent strain of the disease they were intended to prevent.

In poultry, a form of herpesvirus (gallid herpesvirus 1) causes a respiratory disease that is sometimes fatal; even if it doesn't kill the animals, it causes a reduced egg production. As a result, several vaccines have been developed against the virus responsible, based on attenuated forms that do not cause serious illness. Three of these vaccines are approved for use in Australia: two based on viral strains that are present in Australia, and a third developed against a strain common in Europe.

As these vaccines were introduced to the Australian poultry population, two previously unidentified viral strains (class 8 and 9) emerged. The timing of their appearance and some initial genetic characterization suggested they were relatives of the attenuated European virus used in the vaccine. A group of researchers isolated samples of the virus and subjected them to whole-genome sequencing in order to determine their origin.

As expected, large portions of the genome were closely related to the attenuated European virus used as a vaccine. But for the class 8 virus, a small portion of the European DNA had been replaced by recombination with another virus. That other virus appeared to be most closely related to the Australian strains used in the other vaccine. A similar thing was found in the genome of the class 9 virus, where an even larger portion of Australian viruses had recombined into the European backbone. The viruses had picked up additional base changes throughout the genomes, but the majority of the sequence appears to be derived from strains used in vaccines.

To confirm that these viruses had really changed sufficiently to cause disease, the authors cultured them in disease-free chickens. Both recombined viruses (class 8 and 9) had either significantly increased virulence or replicated much more efficiently than the parental strains used in vaccines.

The risks created by the use of related attenuated viruses are well understood both on the level of molecular biology and in terms of evolutionary principles. But the clear demonstration that the risk has become a reality makes this finding an important caution. "The findings from this study raise concerns about the use of multiple distinct attenuated herpesvirus vaccines under conditions that favor recombination," the authors conclude. "These findings have implications for the use of herpesviruses, and possibly other DNA viruses, as attenuated vaccines or vaccine vectors."

Was the new virus formed when a) two virus were combined in a lab to form one new vaccine, or b) was the new virus formed when two vaccines where given to a single animal in the barnc) was the new virus formed when two vaccines where given to different animals in the barn

And of course, what is the likelihood this would be seen in a human population?

Was the new virus formed when a) two virus were combined in a lab to form one new vaccine, or b) was the new virus formed when two vaccines where given to a single animal in the barnc) was the new virus formed when two vaccines where given to different animals in the barn

My understanding is that it's not yet completely clear, but appears to be a case of b) or c). This study began *because* these new strains started showing up in the wild (so to speak).

These are how the chickens and all poultry have to be treated, in free wandering space, with good health practices and as naturally as possible. Not like those companies which jam multiple chickens in small cages in terrible conditions. Same goes to cows, pigs in muddied areas with excretion all over.

The real question is, if this new strain was created by parts of the two vaccines interacting:

Was the immunity that the two vaccines provided bypassed, or was it chickens with only one (or neither) vaccine that could be infected? Would the chicken treated with both vaccines be immune to the new hybrid strain?

It definitely has nothing to do with the conditions poultry and livestock are raised in. Rather than improve conditions in order to reduce the need for antibiotics and vaccines, we must vaccinate for the vaccine!

"When it comes to viruses, one-in-a-million events happen all the time"

Considering the incomprehensibly large number critters in for example the human microbiome [http://en.wikipedia.org/wiki/Human_microbiome] I'd venture to say one-in-a-billion events happen all the time.

"When it comes to viruses, one-in-a-million events happen all the time, and evolution gives any viruses used in vaccines a lot to work with: many related viruses in the wild, and animal genomes that are littered with pieces of former viruses."

In the previous sentence "evolution" seems to be used incorrectly.

Evolution doesn't give or do anything (neither does natural selection in this scenario). Mutation is what gives viruses a lot to work with. Also, incidentally it would be the variety of viruses (from the mutations) that give evolution a lot to work with. Evolution is the end result after the work has happened.